Il-2Rβ-selective agonists in combination with an anti-CTLA-4 antibody or an anti-PD-1 antibody

1. A method of treating a patient suffering from a solid cancer, the method comprising the steps of: (a) administering to the patient an IL-2Rβ-activating amount of a long acting, interleukin-2 receptor beta (IL-2Rβ)-selective agonist of a formula:

or a pharmaceutically acceptable salt form thereof, wherein IL-2 is an interleukin-2, and (n) ranges from 3 to 4,000; and (b) administering to the patient a PD-1 pathway-inhibiting amount of an anti-PD-1 antibody, wherein step (a) is carried out before, after or simultaneously with step (b).

2. The method of claim 1 , wherein the patient is a human.

3. The method of claim 1 , wherein the cancer is melanoma.

4. The method of claim 2 , wherein the solid cancer is selected from the group consisting of breast cancer, ovarian cancer, colon cancer, colorectal cancer, gastric cancer, malignant melanoma, liver cancer, small cell lung cancer, non-small cell lung cancer, thyroid cancers, kidney cancer, cancer of the bile duct, brain cancer, cervical cancer, maxillary sinus cancer, bladder cancer, esophageal cancer, Hodgkin's disease and adrenocortical cancer.

5. The method of claim 1 , wherein the cancer is colon cancer.

6. The method of claim 1 , wherein the cancer is breast cancer.

7. The method of claim 1 , wherein step (a) is carried out prior to step (b) being carried out.

8. The method of claim 1 , wherein step (a) is carried out after step (b) is carried out.

9. The method of claim 1 , wherein steps (a) and (b) are carried out simultaneously.

10. The method of claim 1 , wherein step (a) comprises parenterally administering to the patient the long acting, interleukin-2 receptor beta (IL-2Rβ)-selective agonist.

11. The method of claim 1 , wherein step (b) comprises parenterally administering to the patient the anti-PD-1 antibody.

12. The method of claim 10 , wherein step (a) comprises intravenous administration of the long acting, interleukin-2 receptor beta (IL-2Rβ)-selective agonist.

13. The method of claim 11 , wherein step (b) comprises intravenous administration of the anti-PD-1 antibody.

14. The method of claim 1 , wherein the long-acting, interleukin-2 receptor beta (IL-2Rβ)-selective agonist comprises no more than ten mole percent of compounds having a formula,

or pharmaceutically acceptable salts thereof, where IL-2 is an interleukin-2, and (n) ranges from 3 to 4,000.

15. The method of claim 14 , wherein the long acting, interleukin-2 receptor beta (IL-2Rβ)-selective agonist comprises no more than five mole percent of compounds having a formula,

or pharmaceutically acceptable salts thereof, where IL-2 is an interleukin-2, and (n) ranges from 3 to 4,000.

16. The method of claim 1 , where the anti-PD-1 antibody is selected from nivolumab, lambrolizumab (pembrolizumab), MDPL3280A (atezolizumab), MEDI4736 (durvalumab) and MSB0010718C (avelumab).

17. The method of claim 1 , wherein each

moiety comprised in the long acting, interleukin-2 receptor beta (IL-2Rβ)-selective agonist has a molecular weight of about 20 kilodaltons.

18. The method of claim 1 , wherein the interleukin-2 is aldesleukin.